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Updated: May 3, 2026
FISH for Pre-implantation Genetic Diagnosis
Published on: February 23, 2011
Optimizing gene panels for equitable reproductive carrier screening: The Goldilocks approach
Mia J Gruzin1, Matthew Hobbs2, Rachel E Ellsworth3
1Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; School of Clinical Medicine, UNSW Medicine and Health, St Vincent's Clinical Healthcare Campus, Darlinghurst, NSW, Australia.
Purpose:
Professional organizations recommend pan-ancestry carrier screening for autosomal recessive and X-linked conditions. Advances in DNA sequencing have allowed the analysis of hundreds of genes; however, the optimal number of genes for carrier screening remains unclear. The American College of Medical Genetics and Genomics (ACMG) has proposed a tiered approach recommending screening for 113 genes.
Methods:
We analyzed ClinVar and gnomAD v4.1.0, for genes associated with serious autosomal recessive and X-linked conditions and modeled screening performance across panels of varying compositions and sizes in diverse genetic ancestries. We also reevaluated the ACMG gene list using the updated gnomAD data.
Results:
We identified potential inconsistencies in the ACMG gene lists, particularly in the carrier test performance (defined as a positive yield) for underrepresented genetic ancestry groups. Modeling of the population data for 1310 genes revealed that the screening of 152, 248, 531, and 725 genes achieved 90%, 95%, 99%, and 99.7% positive yields, respectively, in couples. Real-world data from the screening of more than 60,000 couples were used to validate the model.
Conclusion:
Our methodology optimizes the gene content of carrier screening panels for diverse ancestry groups, provides a mechanism for continually updating guidelines, ensures consistency with genomic population data, and improves equity across populations.
